Array centrifuge

ABSTRACT

The present invention is directed to a microcentrifuge apparatus adapted to simultaneously spin a plurality of samples contained within a plurality of rotors. The microcentrifuge comprises an upper plate that has a plurality of upper plate holes; and a lower plate that has a plurality of lower plate holes or recesses. The lower plate is adjacent and substantially parallel to the upper plate, and the plurality of lower plate holes or recesses are in axial alignment with the plurality of upper plate holes. The plurality of rotors are adapted for retaining and spinning the plurality of samples, and are positioned between the upper plate and the lower plate. Each of the plurality of rotors has at opposing ends an upper shaft and a lower shaft, wherein the upper shaft engages one of the upper plate holes and the lower shaft engages one of the lower plate holes or recesses such that the axes of rotation of each of the plurality rotors are substantially perpendicular to the upper and lower plates. In addition, each of the rotors has a central outer surface portion positioned between the upper and lower plates, wherein the central outer surface portion is outwardly bulged. The microcentrifuge further comprises a pulley and a drive belt that is operatively engaged with the pulley and the bulged central outer surface portion of each of the plurality of rotors.

This application claims the benefit of U. S. Provisional Application No.60/118,013, filed Jan. 29, 1999.

STATEMENT OF GOVERNMENT INTEREST

This invention was made with government support under Grant Nos.HG02125-01 and HG02125-02 awarded by The National Human Genome ResearchInstitute. The government may have certain rights in this invention.

TECHNICAL FIELD

This invention relates generally to microcentrifugation instruments andtechniques, specifically to an improved arrayable microcentrifuge forsimultaneous centrifugation of samples.

BACKGROUND OF THE INVENTION

Centrifugation as a means of accelerating sedimentation of precipitatesand particulates has long been an integral part of biochemicalprotocols. A typical centrifuge consists of a rotor encased in ahousing. The rotor is powered by a drive motor or some other force thatallows it to complete a set number of rotations per minute (rpm).Attached to the rotor are holders in which to place sample containers,such as test tubes or well plates. These holders are placedsymmetrically around the circumference of the rotor. The samplecontainers are balanced to insure a symmetric mass distribution aroundthe rotor. The sample containers are placed in the holders and thesamples can then be spun and separated.

Separation of the samples occurs because each component has a differentdensity and thus a different sedimentation velocity. Sedimentationvelocity is a measure of how fast a component will migrate through othermore buoyant sample components as a result of the centrifugal fieldgenerated by the centrifuge.

Using centrifugation, a variety of samples can be separated. Specifictypes of cell organelles can be isolated, particles can be removed froma suspension, and different liquids in a solution can be separated. Theamount of separation of a sample is determined by the rpm used and thelength of time the sample is spun. Recently, the increasing demand forhigh-throughput assays in the field of biochemistry has created a needfor parallel processing and automation of many such protocols. Standardcentrifuges have proven to be incompatible with these needs.

The need for highly parallel sample processing has led the sciencecommunity to usage of multiwell plates. Because of the plates'insufficient mechanical strength, centrifugation of samples held in suchplates is limited to accelerations below 3,500×g. Furthermore, multiwellplate centrifuges are large and cumbersome to automate. Thoughautomation of centrifuge-based sample preparation has been performed(AutoGen 740, AutoGen, Framingham, Mass.), the resulting instrumentshave limits (<96 samples/hr per instrument) as a result of thesedifficulties.

Filter-based separation protocols also have been automated by severalcompanies (Qiagen, Chatsworth, Calif., and Beckman Coulter, Palo Alto,Calif) but also are limited in throughput (roughly 96 samples/hr perinstrument) and are at least 10 times more expensive thancentrifuge-based separations.

The main limitations of centrifuges are 1) the need for a large amountof manual labor to load and unload them, 2) the small number of samplesthat can be spun down at one time, and 3) the length of time it takes tospin down samples. In addition, the maximum acceleration used in currentcentrifuges is limited by the mechanical strength of the samplecontainers, particularly multi-well plates, which increases the amountof time needed to spin down samples. Although these problems could beovercome by the use of robotic arms and the purchase of morecentrifuges, the cost and space requirements would be prohibitive formost laboratories.

PCT Application No. PCT/US98/18930 (published as InternationalPublication No. WO 99/12651) addresses some of these problems bydisclosing a high-throughput centrifugation system in which samples arespun directly in contact with individual, miniature rotors rather than asample holder. However, this system does not disclose an efficient meansfor the simultaneous rotation and restraint of the rotors. Moreover,this application does not disclose an efficient means for containingsamples and protecting the apparatus from spillage. What is needed is areliable and efficient high-throughput automated centrifugationapparatus.

SUMMARY OF THE INVENTION

In one embodiment, a microcentrifuge apparatus has a plurality of rotorsfor simultaneously spinning a plurality of samples; a retainer forretaining each of the rotors on a bearing surface; and at least onesource of motive power (i.e., a motor), coupled to the rotors by acoupling means, for causing each of the rotors to spin at substantiallythe same rate. The coupling means is preferably a drive belt such as asingle continuous drive belt.

In another embodiment, the microcentrifuge apparatus has a plurality ofrotors for spinning a plurality of samples; a retainer for retainingeach of the rotors on a bearing surface; at least one source of motivepower for spinning the rotors; and at least one drive belt, coupledbetween the power source and each of the rotors, for applying the motivepower to each of the rotors.

In another embodiment, the microcentrifuge has a plurality of rotors,each having a longitudinal axis and each containing a sample, aplurality of retainers for retaining each rotor at its predeterminedlocation; a bearing surface located at each predetermined location forsupporting each rotor as it is spun; and a source of rotating powercoupled to the rotors for spinning each rotor on its longitudinal axis.

In another embodiment, the micro-array centrifuge has the following: a.a lower plate with a plurality of recesses; b. an upper plate with aplurality of holes, each hole lined by a raised cuff; c. a plurality ofrotors, each having a longitudinal axis, top, bottom, crown, side andupper shaft, the side and crown maintaining contact with a drive belt;d. a motor for moving the drive belt, which in turn spins the rotorsabout their longitudinal axes; e. a cap with an inner and an outer lip,the inner lip adhering to the upper shaft and the outer lip beingoutside of the raised cuff and in close proximity to the top surface ofthe top plate, whereby fluid is prevented from getting into themicroarray centrifuge; and f. each rotor bottom contacting at least onebearing which contacts at least one recess in the lower plate.

In another embodiment, the microcentrifuge has a lower plate dividedinto strips, each of which is anchored at its end.

In another embodiment, the microcentrifuge has a plurality of disposablerotors for simultaneously spinning a plurality of samples, a retainerfor retaining each of the rotors on a bearing surface; and a source ofmotive power, coupled to the rotors, for spinning each of the rotors atsubstantially the same rate. The disposable rotors fit into and areremovable Prom a plurality of rotor encasements of the array centrifuge.The disposable rotors comprise one or more chambers for samples.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is an overview of a microcentrifuge.

FIG. 2 is an overview of the microcentrifuge after the cover has beenremoved.

FIG. 3 is an overview of the microcentrifuge of FIG. 2 with anexaggerated belt for purposes of illustration.

FIG. 4A is a cross-sectional view of a row of 12 centrifuge rotors.

FIG. 4B is an enlargement of area B of FIG. 4A.

FIG. 5 is an overview of the top cover plate of the centrifuge thatshows pins to align other tools.

FIG. 6A shows the bottom half of the rotor.

FIG. 6B shows the top half of the rotor.

FIG. 6C is a cross-sectional view of FIG. 6A showing the slight bulge orcrown of the bottom half of the rotor.

FIG. 7 illustrates a second embodiment of the microcentrifuge that canaccommodate two motors.

FIG. 8 illustrates the eight “strips” that comprise the lower plate ofthe second embodiment and can accommodate 12 rotors each.

FIG. 9 highlights the path of two belts in the second embodiment of themicrocentrifuge.

FIG. 10 is a partial cross-sectional view of a disposable rotorembodiment.

FIG. 11A is a top view of the disposable rotor with spacers.

FIG. 11B is a cross-sectional view of the disposable rotors withspacers.

DETAILED DESCRIPTION OF THE INVENTION

One of the best ways to address the need for highly parallel sampleprocessing in the field of biotechnology is a high-throughputcentrifugation system in which samples are spun directly in contact withindividual, miniature rotors rather than with a sample holder. One suchsystem is disclosed in PCT Application No. PCT/US98/18930 (published asInternational Publication No. WO 99/12651). The application disclosesthe preferred embodiment of using a fluid stream to spin the rotors ontheir longitudinal axis, wherein the transferring momentum comprises aset of indentations in an exterior surface of each rotor. However, dueto variable bearing friction, it is difficult to obtain uniformity ofrotation rates from rotor to rotor especially over a wide range ofvelocities using a high velocity fluid stream as a means of driving therotors. This difficulty arises due to the variation of the friction frombearing to bearing in the ball bearings used to retain the rotors andresults in widely varying steady state rotational velocities of therotors.

The present invention discloses an improved high-thoroughput, automatedcentrifuge. Similar to the invention disclosed above, it is a centrifugein which samples are spun directly in contact with individual, miniaturerotors rather than with a sample holder. However, instead of poweringthe rotors with a fluid stream, the present invention discloses a sourceof motive power, such as a motor, coupled to the rotors by variousmechanical coupling means. This configuration provides for precise,uniform rotational velocity of the rotors across the entire array ofrotors for a wide range of velocities and helps keep the rotors inplace. The invention further discloses a means of restraining the rotorsusing lubricated bearings and a bearing surface. Another advantage isthe addition of a resilient ring between the lubricated bearings and thebearing surface for providing consistent pre-load for the bearings aswell as noise reduction.

In FIG. 1, an exemplary microcentrifuge 100 has an upper plate 102 and alower plate 104, both of which enclose a plurality of rotors (notshown). A preferred material for the upper and lower plates 102, 104 isaluminum. The lower plate 104 may have a solid bottom, or it may haveholes (not shown) under any and all the rotors (not shown) and theirrespective bearings (not shown). The upper plate 102 has a plurality ofholes 106 surrounded by raised cuffs 108, which in turn surround therotors (not shown). The upper plate 102 is connected to the lower plate104 by a plurality of screws (not shown) located on the periphery of theupper plate 102 within a plurality of screw holes 110. The upper plate102 also has a plurality of instrument alignment holes 112 toaccommodate alignment pins (not shown) associated with otherinstruments, such as for example a pipetter used for dispensing andaspirating samples into the rotors (not shown). An air inlet hole 114lets in air for passive cooling; for more effective cooling or heating,a tube (not shown) may be attached to a fitting (not shown) at the airinlet hole 114 such that heated or cooled air may be delivered to themicrocentrifuge 100. An open slot 116 may be used for a speed sensor(not shown) that monitors the rotational rate of the rotors (not shown)and ensures that the rotors are moving at the correct rate. A pluralityof drainage slots 118 are located on the upper plate 102 allow fordrainage if there is spillage of the samples. FIG. 1 also illustrates apulley cover plate 120 that covers a pulley (not shown) and protects itfrom outside elements. The pulley cover plate 120 is preferably made outof a machinable metal, such as anodized aluminum.

FIG. 2 shows the microcentrifuge 100 of FIG. 1, but with the upper andpulley cover plates 102, 120 removed thereby showing the placement ofthe plurality of rotors 220. As shown, each of the plurality of rotors220 has an upwardly protruding shaft portion 222. Also shown is thepulley 224 that is driven by a DC motor (not shown). A controller (notshown) connects the motor and a remote computer (not shown), whichdetermines when and how fast the rotors 220 will spin.

FIG. 3 shows the path that a belt 326 takes around the pulley 224 androtors 220. The belt 326 may be made from a variety of materials thattolerate temperature change and avoid stretching. Preferably the belt326 is made of KAPTON polyimide tape (DuPont, Wilmington, Del.). In thisconfiguration, the belt 326 is 61 inches in length, 0.250 inches wideand 0.003 inches thick. The belt 326 is held in place by a rotor “crown”(not shown) associated with the lower rotor (not shown), as discussedbelow. The belt 326 is further held in place by a pulley “crown” (notshown) associated with the pulley 224, which crown is a slight concavebulge with a radius of curvature of approximately 4.5 inches around thecircumference of the outer surface of the pulley 224.

FIG. 4A is a cross section of twelve of the plurality of rotors 220.Circle “B” of FIG. 4A has been exploded in FIG. 4B. FIG. 4B shows thedetails of the assembly of each rotor 220, including the cooperationbetween rotors 220 and upper plate 102 (wherein a secure seal is formedthat protects the inside of the microcentrifuge from fluid contaminationand corrosion). Each of the plurality of rotors 220 may be fabricated intwo parts: an upper rotor half 428 and a lower rotor half 430. Therotors 220 are further discussed below. The upper rotor half 428includes the upwardly protruding shaft portion 222 (also shown in FIG.2), wherein each shaft portion 222 is covered with a cap 432. The cap432 is preferably made of TEFLON (DuPont, Wilmington, Del.). The cap 432has an inner lip 434 and an outer lip 436. The inner lip 434 is flushwith the upwardly protruding shaft portion 222 so as to form a tightseal. The outer lip 436 is positioned outside the raised cuff 108 ofupper plate 102 and ends just above the upper plate 102, leaving anarrow space 438 (surface tension associated with a spilled fluidprevents any fluid from entering around the outside of the rotor).

Between upper plate 102 and upwardly protruding shaft portion 222 is abearing 440, which presses on the shoulder 442 of upper rotor half 428for controlled turning. Each bearing 440 is preferably lubricated andmade of stainless steel, with a plastic retainer made of polyimide(DuPont, Wilmington, Del.). There may also be an optional O-ring 444 toabsorb sound and to preload the bearings and decrease radial and axialmovement. Each O-ring 444 is preferably made of silicone rubber. Atlocation 446, outside the cap 432, an absorbent material (not shown) mayalso be placed to attenuate noise. Preferred is a sponge-like materialor a fibrous mat with 96 holes or any other appropriate number cut outto accommodate the rotors 220, which can be easily removed and replaced.

FIG. 5 illustrates a top cover plate 548 having a plurality of sampleinlet holes 550 to match up with the array of rotors (not shown). Thetop cover plate 548 holds the caps (not shown) in place duringcentrifugation. The top cover plate 548 is preferably made of amachinable plastic, such as a polycarbonate or acrylic plastic. Alsoillustrated are three alignment pins 552 that help align otherinstruments, such as for example a pipetter, with the plurality ofsample inlet holes 550.

FIG. 6A, FIG. 6B, and FIG. 6C provide detail of the upper half 428 andthe lower half 430 of each of the plurality of rotors, both outside andinside. Each rotor is preferably made from strong, non-reactive materialsuch as titanium. On the lower half 430 and as best seen in FIGS. 6A and6B, there is a “crown” 654, which constitutes a slight concave bulgewith a radius of curvature of approximately 7 inches around thecircumference of the outer surface of the rotor. The belt (not shown)seeks the highest point of the crown 654 such that the belt stayscentered on the rotor and keeps it from sliding off its track.

FIG. 7 shows a top view of a second embodiment of the micro-arraycentrifuge of the present invention. In this configuration, the arraycentrifuge 700 has two motors (not shown). It is modular and can easilybe moved to various desired locations in a workspace. In this embodimentthere is no upper plate; rather the array centrifuge 700 includes anenclosure, preferably comprised of one piece. This solid configurationprovides stability and sound abatement. FIG. 7 also illustrates a shelf702 for spillage of the samples.

FIG. 8 shows a bottom of the second embodiment, wherein the lower meansfor retaining the rotors (not shown) include 8 separate “strips” 804that form a lower plate. Each strip 804 has a plurality of bottom holes806 that hold 12 rotors (not shown) in place. Providing multiple stripssignificantly decreases the planar movement of the rotors that can occurin a solid lower plate that holds all 96 rotors. Each strip has endscrew holes 808 for screws to securely anchor each strip.

FIG. 9 illustrates how each of the two motors (not shown) associatedwith the second embodiment combine with two pulleys 910, 912 and twobelts 914, 916 (each belt drives one half of the array). Each motor isconnected to a remote computer (not shown) by a controller (also notshown), which determines when and how fast the rotors 918 will spin. Thetwo belts 914, 916 are each weaved around its respective pulley 910, 912and around one half of the plurality of rotors 918. The spinning of thepulleys 910, 912 moves the belts 914, 916 and in turn spins the array ofrotors 918. The use of two motors lowers the power requirements of eachmotor thereby increasing their lives and centrifuge reliability.Moreover, in this second embodiment of the invention, the two belts 914,916 each wraps around more surface area of its respective pulley 910,912 (such differences in configuration may be observed by comparingFIGS. 9 and 3). The larger surface area results in a lower likelihoodfor belt slippage.

It can be seen that a 96-channel pipetter will work with the 96-wellmicro-array centrifuge. The advantages of the microcentrifuge are many.Because the rotors are so small, there is less mass to overcome inacceleration and deceleration. Hence, the rotors can accelerate rapidlyto a speed of 2,000 revolutions and stop very quickly. Themicrocentrifuge takes up very little room and uses very little energy.Due to the small size and mass of the rotors, very high centrifugationforces can be achieved, on the order of 14,000 times the force ofgravity and therefore very short sedimentation times can be obtained.

In another embodiment, various coatings, such as TEFLON orpolypropylene, of the rotor interior provide optimal pellet retentionand easy cleaning of the rotors.

In another embodiment of the microcentrifuge apparatus, the rotors arecoupled to the source of motive power by a drive belt, wherein thesource of motive power may be a motor or engine.

In another embodiment, the rotors are controlled by electromagneticmeans. Each rotor effectively becomes an individual motor. A shaft isattached and extends out from the rotor. The shaft is surrounded byelectrically conductive wire windings. A circular magnet surrounds thesewindings and is held in place by a retaining plate. The ends of the wirewindings are attached to commutators. The commutators are contacted byelectrically conductive metal brushes. Electrical current from the motorcontrol source is supplied through the brushes to the windings toproduce alternating magnetic fields. The interaction of this alternatingmagnetic field with the stationary circular magnet produces torque onthe shaft that drives the circular rotation of the rotor. The samecontrol voltage can be applied to all motors allowing all rotors torotate at the same speed. Additionally, each motor can be controlledindividually allowing each rotor to achieve different rotational speeds.

In another embodiment of the array centrifuge, the rotors aredisposable. The use of disposable rotors avoids the problem of thecross-contamination of samples. The rotors fit into an independent drivetrain comprised of a plurality of permanent rotor encasements and amotive means. Each sample is processed in its own unique disposablerotor and is replaced before a new sample is introduced. This avoids theneed for washing out the rotors between samples and saves processingtime.

FIG. 10 illustrates the preferred embodiment of the apparatus withdisposable rotors. The disposable rotors are preferably made of a toughnon-reactive material such as polypropylene. Each disposable rotor 400fits snugly into a rotor encasement 402 of the array centrifuge. Theencasement is preferably made from strong material such as titanium. Therotor encasement 402 has at least one opening 404 into which adisposable rotor 400 may be inserted. The lower portion of the rotorencasement has a shaft 406 that fits into one or more bearings 408 thataccommodate the movement of the rotor encasement 402. The bearings 408are preferably lubricated and comprised of stainless steel, with aplastic retainer made of polyamide (DuPont, Wilmington, Del.). Eachbearing 408 has at least one retaining plate 410 to hold the bearing 408in place. There may also be an optional O-ring 412 between the lowerportion of the rotor encasement 402 and the retaining plate 410 toabsorb sound and preload the bearings 408 and decrease radial and axialmovement. The O-rings 412 are preferably made of silicone rubber.

Directly below the first bearing 408, a pulley 416 is wrapped around theshaft 406 of the rotor encasement 402. A belt 418 may be woven aroundeach pulley 416 in the array of rotor encasements 402 for motion. Thebelt 418 is actuated by a motive means, such as a motor (not shown) andan independent pulley (not shown). Beneath the pulley 416 is a secondlubricated bearing 420 and at least one retaining plate 411 to keep thebearing 420 in place. Optionally, an O-ring 412 may be used to absorbsound and preload the bearings 420 and decrease radial and axialmovement.

Figures 11A and 11B illustrates yet another embodiment of disposablerotors for an array centrifuge. The disposable rotor 400 includesspacers 422 on the outside of the rotor 400 as shown in FIG. 11 A. Thespacers 422 maintain a pocket between the rotor 400 and the rotorencasement 402. FIG. 11B illustrates that the rotor 400 is shorter inlength than the rotor encasement 402 which creates a space between thebottom of the rotor 400 and the rotor encasement 402. This design allowsfor spillage of the samples to drain down the sides of the rotor 400 andout the bottom of the shaft 406 to avoid sample contact with themechanical parts of the apparatus. Sample contact with the mechanicalparts of the apparatus, such as the belt 418 or pulley 416, couldcorrode parts.

In another embodiment of disposable rotors, the rotors have one or morechambers for the retention of samples. This embodiment of the rotordecreases the likelihood of cross-contamination in sample preparations.The chambers are stacked on top of one another inside the disposablerotor. Each chamber, for example, can contain a sample, a precipitationagent, a buffer, and a mixing reagent or other liquid necessary for aparticular protocol. An entire cell preparation can be accomplishedwithout the sample ever leaving the rotor's chamber.

For example, a rotor with a first chamber containing plasmid DNA and itshost E. coli cells suspended in a growth media and a second chambercontaining a precipitation agent could be used to isolate DNA. The rotoris centrifuged and a cell pellet containing the DNA forms on wall of therotor. At the end of centrifugation, supernatant is collected at thebottom of the rotor. The supernatant is aspirated from the firstchamber. A re-suspension reagent, a lysis buffer and a neutralizationbuffer are each added individually, mixed with the DNA and its host E.coli cells and centrifuged. After this process is completed, a pelletmade up of flocculants, such as a cell membrane, mitochondria, and othercell organelles, is formed on the wall of the first chamber and plasmidDNA is dissolved in the lysate at the bottom of the chamber. Typically,the next step in the isolation of DNA is removing the lysate containingthe plasmid DNA and replacing or cleaning out the rotors before the DNAis further purified. In this embodiment of rotors, the lower half of thefirst chamber is punctured, and the lysate containing the DNA flowsthrough into the second chamber leaving the pelletted flocculantsbehind. The precipitation agent in the second chamber is then mixed withthe lysate containing the plasmid DNA. The centrifuge is actuated andspins the rotor, forming a DNA pellet on the wall of the rotor. When thecentrifuge is brought to a standstill, there is a DNA pellet on the walland alcohol at the bottom of the rotor. The alcohol is removed. 70%ethanol is added to wash the DNA. The mixture of 70% ethanol and DNA iscentrifuged and the excess ethanol is removed. Water is added and theDNA is resuspended in it. This process results in purified DNA suspendedin water with less likelihood of cross-contamination of the samples.

EXAMPLE 1 Plasmid DNA Isolation

The disclosed array centrifuge can be used in conjunction with a roboticworkstation for the automated isolation of plasmid DNA (RevPrep™,GeneMachines, San Carlos, Calif.). The workstation includes, but is notlimited to, a bulk reagent dispenser, a 96-channel pipetter, a serverarm and the disclosed array centrifuge. All tools are available fromGeneMachines, San Carlos, Calif. The workstation has a base, a deck, anda support column. In this configuration, the bulk reagent dispenser and96-channel pipetter are connected to the support column, on which theymove vertically. The disclosed array centrifuge and a wash station arebolted to the rotary deck, and at least one microwell plate sits on thedeck, which moves the items thereon horizontally to interact with thetools on the column. LabVIEW™ Software (National Instruments™, Austin,Tex.) is programmed to run this configuration of the roboticworkstation.

Plasmid DNA and its host E. coli cells suspended in a growth media arecontained in a plurality of wells of a microwell plate. The microwellplate is placed on the deck of robotic workstation by a robotic serverarm. The deck moves horizontally until the microwell plate is preciselyaligned with the pipetter. The pipetter is vertically moved toward thedeck, and it aspirates the samples of growth media and cloned plasmidDNA from the microwell plate. The pipetter is then moved to its originalposition.

The array centrifuge is located on the deck of the robotic workstation.The deck moves horizontally until the array centrifuge is preciselyaligned with the pipetter. The pipetter is vertically moved toward thearray centrifuge and deposits the samples into a plurality of rotors ofthe array centrifuge. The pipetter is then moved back to its originallocation. The array centrifuge is actuated, and the rotational rate ofthe rotors is increased from a standstill position to a maximumrotational rate of around 60,000 rpm in 20 seconds. This rotational rateis maintained for approximately 30 to 40 seconds. During this time, thecell pellet, forms on the interior wall of the rotor, and thesupernatant with the plasmids collects towards the center of the rotor.The rotational rate is steadily decreased to a standstill over a periodof two minutes and the supernatant is collected at the bottom of therotor. This length of time limits turbulence and accidentalre-suspension of the cells. The pipetter is then vertically movedtowards the array centrifuge, the supernatant is aspirated, and thepipetter vertically moves back to its original position.

The deck then moves horizontally until the array centrifuge is preciselyaligned with the bulk reagent dispenser. The dispenser moves verticallytoward the array centrifuge and dispenses a resuspension reagent intothe array of centrifuge rotors. The centrifuge rotors are rapidlyaccelerated and decelerated to resuspend the cells in the resuspensionreagent. Twenty-five acceleration/deceleration cycles occur in as few as20 seconds with the rotors approaching a top speed of about 20,000 rpm.Meanwhile, the bulk reagent dispenser has obtained and introduces Lysisbuffer into the array of centrifuge rotors. The bulk reagent dispenseris then moved to its original position, while the rotors are then gentlyaccelerated and decelerated to mix the re-suspended cells and the lysisbuffer without disrupting the plasmid DNA, yet lysing cell membranes.The mixture is incubated for 3 to 5 minutes.

In the meantime, the bulk reagent dispenser has moved to the washstation where it rinses the pipette tips and aspirates neutralizingbuffer. As the array centrifuge slows, it is moved to the pipetter,which dispenses neutralization buffer into the array of centrifugerotors after it has come to a complete stop. The mixture is gently mixedby accelerating and decelerating the rotors and then incubated for 3 to5 minutes. This brings the pH back to neutral before the plasmid DNA isdenatured. The array centrifuge is actuated and the rotational rate ofthe rotors is increased from a standstill position to a maximumrotational rate of around 60,000 rpm in 20 seconds. This rotational rateis maintained for approximately 1 minute. The rotational rate issteadily decreased to a standstill over a period of two minutes.

A pellet forms on the interior wall of each centrifuge rotor and is madeup of flocculants such as cell membranes, mitochondria, and othercellular organelles. Plasmid DNA dissolved in the lysate is located atthe bottom of each rotor. Alcohol precipitation and centrifugation mayfurther purify the plasmid DNA.

It is to be understood that the description above is intended to beillustrative and not restrictive. Many embodiments will be apparent tothose of skill in the art upon reviewing the above description. Thescope of the invention should be determined not with reference to theabove description but should instead be determined with reference to theappended claims, along with the full scope of equivalents to which suchclaims are entitled.

While the invention has been described in some detail by way ofillustration, the invention is amenable to various modification andalternative forms, and is not restricted to the specific embodiments setforth. These specific embodiments are not intended to limit theinvention but, on the contrary, the intention is intended to cover allmodifications, equivalents, and alternatives falling within the spiritand scope of the invention.

We claim:
 1. A micro-array centrifuge comprising: a lower plate with aplurality of recesses; an upper plate with a plurality of holes, eachhole lined by a raised cuff; a plurality of rotors, each having alongitudinal axis, top bottom, crown, side and an upper shaft, the sideand crown maintaining contact with a drive belt; a cap with an inner andan outer lip, the inner lip adhering to the upper shaft and the outerlip being outside of the raised cuff and in close proximity to the topsurface of the upper plate, whereby fluid is prevented from getting intothe microarray centrifuge; and each rotor bottom contacting at least onebearing which contacts at least one of the plurality of recesses of thelower plate.
 2. The microcentrifuge of claim 1, wherein the lower platecomprises a series of strips, each of which is anchored at its end.
 3. Amicrocentrifuge apparatus adapted to simultaneously spin a plurality ofsamples, comprising: an upper plate having a plurality of upper plateholes a lower plate having a plurality of lower plate holes or recesses,wherein the lower plate is adjacent and substantially parallel to theupper plate, and wherein the plurality of lower plate holes or recessesare in axial alignment with the plurality of upper plate holes; aplurality of rotors for retaining and spinning the plurality of samples,wherein the plurality of rotors are positioned between the upper plateand the lower plate, and wherein each of the plurality of rotors has atopposing ends an upper shaft and a lower shaft, wherein the upper shaftof each of the plurality of rotors engages one of the upper plate holesand wherein the lower shaft of each of the plurality of rotors engagesone of the lower plate holes or recesses such that the axes of rotationof each of the plurality rotors are substantially perpendicular to theupper and lower plates, and wherein each of the rotors has a centralouter surface portion positioned between the upper and lower plates,wherein the central outer surface portion is outwardly bulged; a pulley,and a drive belt operatively engaged with the pulley and the centralouter surface portion of each of the plurality of rotors.
 4. Themicrocentrifuge apparatus of claim 3, wherein the outwardly bulgedcentral outer surface portion of each rotor is concave.